Cytokine receptor-like factor 3 (CRLF3)

Cytokine receptor-like factor 3 (CRLF3) is an evolutionarily conserved orphan class I cytokine receptor expressed predominantly in neural and hematopoietic cells. It appears structurally and functionally homologous to other class I cytokine receptors, containing a fibronectin type III domain with a WSXWS motif and a SPRY protein interaction domain. CRLF3 has been implicated in signal transduction, notably JAK–STAT signaling, cell cycle regulation, neuroprotection, neuronal development, synaptic vesicle biogenesis, and the maturation of blood cells, including platelets and erythrocytes. Its dysregulation is associated with neurological disorders, cancer, and blood cell development abnormalities. The most clearly identified ligand is the splice variant EV-3 of erythropoietin, which mediates neuroprotective effects through CRLF3. Despite advances, the precise physiological functions, ligand spectrum, and therapeutic relevance of CRLF3 remain incompletely understood, and it is considered an orphan receptor with intriguing but emerging biomedical significance[1][2][3][5][7][8].

Other names

CREME9CRLM9CYTOR4P48CREME-9Cytokine receptor-like molecule 9Cytokine receptor-related protein 4Type I cytokine receptor-like factor p48FRWSp48.2

Ligand binding (EV-3, a splice variant of erythropoietin) promotes neuroprotection by inhibiting apoptosis and modulating expression of pro- and anti-apoptotic genes. Potential involvement in JAK–STAT signaling pathway